crossing96/oncoscreening huggingface dataset:
The Epitope Basis of Embryonic Stem Cell-Induced Antitumor Immunity against Bladder Cancer.	Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) share many cellular and molecular features with cancer cells. Taking advantage of these similarities, stem cells are effective vaccines against cancers in animal models. However, the molecular basis is not well understood, which hinders the development of effective cancer vaccines. Here, prophylactic and therapeutic bladder cancer vaccines composed of allogeneic ESCs and CpG with or without granulocyte macrophage colony stimulating factor are tested. The ESC-based cancer vaccines are able to induce specific antitumor immunity including stimulating cytotoxic CD8(+) T cells and memory CD4(+) T cells, reducing myeloid-derived suppressor cells, and preventing bladder cancer growth in mouse models. Furthermore, several genes that are overexpressed in both ESCs and tumors are identified. An epitope-based vaccine designed with shared overexpressed proteins induces specific antitumor immunity and reduces bladder cancer growth. Functional epitopes underlying the action of stem cell-based vaccines against bladder cancer are identified and it is confirmed that ESC-based anticancer vaccines have great potential. A systematic approach is provided here to developing novel effective epitope-based cancer vaccines in the future.	bladder
Cytoreductive Surgery in Patients with Urothelial Bladder Cancer.	Cytoreductive cystectomy appears to have survival advantages as a part of multimodal approach for well-selected patients with bladder cancer. Patient with clinical lymph node metastases might benefit from surgical consolidation after achieving a measurable response to chemotherapy. The exact role of cytoreductive/consolidative cystectomy is yet to be determined in well-designed prospective trials.	bladder
Genomic and Clinical Prognostic Factors in Patients With Advanced Urothelial Carcinoma Receiving Immune Checkpoint Inhibitors.	BACKGROUND: Recently data suggest that telomerase reverse transcripatase (TERT) promoter mutations portend superior outcomes with immune checkpoint inhibitor (ICI) therapy in mUC. In our retrospective analysis from 2 tertiary cancer centers, we assessed the predictive role of TERT mutations along with other parameters. METHODS: Patient registries were queried for patients treated with ICI for mUC with available genomic and clinical data. Select clinical and laboratory parameters, in addition to primary tumor site, histology, treatment modality, and setting were recorded. Tumor mutational burden (TMB), and mutational status of TERT, CDKN2A, CDKN2B, TMB, TP53, RB1, KMT2D, ARID1A, ERBB2, KDM6A, PIK3CA, FGFR3, and ATM were noted. Univariate analysis of significance concerning overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) was conducted. RESULTS: In total, 113 patients were found to meet inclusion criteria. In our study, ORR was 55%, median PFS was 5.1 months (0.2-71.8), and median OS was 13.4 months (0.2-84.8). On univariate analysis, female sex, NLR>5, and ATM mutation were associated with inferior PFS and OS, whereas upper tract primary disease and ECOG score ≥ 2 were associated with worse OS. On multivariate analysis, NLR >5 was associated with worse PFS and OS whereas upper tract primary disease, albumin <3.4 g/dL, hemoglobin <10 g/dL and ATM mutation were significantly associated with worse OS on multivariate analysis. No significant differences were seen in ORR, PFS, or OS regarding TERT promoter mutations. CONCLUSION: TERT promoter mutations were not significantly associated with any difference in outcome in patients treated with ICI.	bladder
Integrated bioinformatic analysis identified a novel prognostic pan-programmed cell death signature for bladder cancer.	"Programmed cell death (PCD) refers to a molecularly regulated form of cell death that functions as an essential anticancer defense mechanism and serves as a target of anticancer therapies. Multiple types of PCD comprehensively regulate tumorigenesis and tumor progression and metastasis. However, a systemic exploration of the multiple types of PCD in cancers, especially bladder cancer, is lacking. In this study, we evaluated the expression pattern of genes associated with multiple types of PCD in bladder cancer using the ""ssGSEA"" method and conceptualized the multiple types of PCD as being collectively involved in ""Pan-PCD"". Based on the differentially expressed genes related to Pan-PCD, we developed a Pan-PCD-related prognostic signature (PPRPS) to predict patient prognosis via univariate and multivariate Cox regression analysis. The PPRPS is an independent prognostic factor, and the AUC (Area Under Curve) for 3-year overall survival was 0.748. Combined with age and stage, PPRPS displayed excellent predictive ability. Based on the PPRPS, higher levels of immune cell infiltration, tumor microenvironment, and immune checkpoint molecules were observed in the high-PPRPS group. Furthermore, PPRPS enabled accurate risk prediction for metastatic urothelial carcinoma after anti-PD-L1 monoclonal antibody treatment. Patients in the high-PPRPS group had poor prognoses. Docetaxel, staurosporine, and luminespib were identified as potentially effective drugs for high-PPRPS bladder cancer patients. In summary, we developed the Pan-PCD signature to improve the accuracy of bladder cancer prognostic predictions and to provide a novel classification method to guide treatment selection."	bladder
Implications of TERT promoter mutations and telomerase activity in solid tumors with a focus on genitourinary cancers.	INTRODUCTION: The reactivation of telomerase represents a key moment in the carcinogenesis process. Mutations in the central promoter region of the telomerase reverse transcriptase (TERT) gene cause telomerase reactivation in approximately 90% of solid tumors. In some of these, its prognostic and predictive role in response to treatments has already been demonstrated, in others (such as tumors of the genitourinary tract like urothelial carcinoma) data are controversial and the research is still ongoing. In the future, TERT promoter mutations and telomerase activity could have diagnostic, prognostic, and therapeutic applications in many types of cancer. AREAS COVERED: We performed a review the literature with the aim of describing the current evidence on the prognostic and predictive role of TERT promoter mutations. In some tumor types, TERT promoter mutations have been associated with a worse prognosis and could have a potential value as biomarkers to guide therapeutic decisions. Mutations in TERT promoter seems to make the tumor particularly immunogenic and more responsive to immunotherapy, although data is controversial. EXPERT OPINION: We described the role of TERT promoter mutations in solid tumors with a particular focus in genitourinary cancers, considering their frequency in this tract.	bladder
Comparison of Laparoscopic and Open Radical Cystectomy for Muscle-Invasive Bladder Cancer.	The goal of the study was to compare laparoscopic and open radical cystectomy in treatment of muscle-invasive bladder cancer in the Department of Urology and Oncological Urology PUM in Szczecin. A total of 78 patients in the study group underwent laparoscopic cystectomy between 2016−2018, and 81 patients from the control group had open cystectomy between 2014−2016. Both groups were comparable in terms of age, stage, and concomitant diseases. The 3 year overall survival was comparable in both groups (37.7% for laparoscopy and 44.4% for open, p = 0.64). There was no difference in positive surgical margin rate. Lymph node yield during cystectomy was higher in open cystectomy (14 vs. 11.5, p = 0.001). Post-operative blood loss and transfusion rates were lower in laparoscopic cystectomy. Decrease in hemoglobin level was lower in laparoscopy (0.9 mmol/L, p < 0.001). Intraoperative transfusion rate was 11.8% in laparoscopy vs. 34.8% in open cystectomy (p = 0.002). Operation time, duration of hospitalisation, and time to full oral alimentation were comparable in both groups. Patients with BMI > 30 kg/m2 and those with pT3-T4 cancer in the laparoscopy group had less septic complications post-operatively. Patients with ASA score ≥ 3 from the laparoscopy group had fewer reoperations due to ileus. Laparoscopic cystectomy is less invasive and offers similar oncological outcomes to the open method. Patients benefit from less tissue trauma, less blood loss, and faster recovery. The presented results, as well as other publications, should encourage a wider use of this procedure in everyday urological practice.	bladder
The BRCAness Landscape of Cancer.	BRCAness refers to the damaged homologous recombination (HR) function due to the defects in HR-involved non-BRCA1/2 genes. BRCAness is the important marker for the use of synthetic lethal-based PARP inhibitor therapy in breast and ovarian cancer treatment. The success provides an opportunity of applying PARP inhibitor therapy to treat other cancer types with BRCAness features. However, systematic knowledge is lack for BRCAness in different cancer types beyond breast and ovarian cancer. We performed a comprehensive characterization for 40 BRCAness-related genes in 33 cancer types with over 10,000 cancer cases, including pathogenic variation, homozygotic deletion, promoter hypermethylation, gene expression, and clinical correlation of BRCAness in each cancer type. Using BRCA1/BRCA2 mutated breast and ovarian cancer as the control, we observed that BRCAness is widely present in multiple cancer types. Based on the sum of the BRCAneass features in each cancer type, we identified the following 21 cancer types as the potential targets for PARPi therapy: adrenocortical carcinoma, bladder urothelial carcinoma, brain lower grade glioma, colon adenocarcinoma, esophageal carcinoma, head and neck squamous carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, mesothelioma, rectum adenocarcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, sarcoma, skin cutaneous melanoma, stomach adenocarcinoma, uterine carcinosarcoma, and uterine corpus endometrial carcinoma.	bladder
Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up.	BACKGROUND: Immune checkpoint inhibitors are a standard therapy in metastatic urothelial carcinoma (UC). Long-term follow-up is necessary to confirm durability of response and identify further safety concerns. PATIENTS AND METHODS: In KEYNOTE-045, patients with metastatic UC that progressed on platinum-containing chemotherapy were randomly assigned 1:1 to receive pembrolizumab or investigator's choice of paclitaxel, docetaxel, or vinflunine. Primary endpoints were progression-free survival per RECIST version 1.1 by blinded independent central review (BICR) and overall survival. In KEYNOTE-052, cisplatin-ineligible patients with metastatic UC received first-line pembrolizumab. The primary endpoint was objective response rate per RECIST version 1.1 by BICR. RESULTS: A total of 542 patients (pembrolizumab, n = 270; chemotherapy, n = 272) were randomly assigned in KEYNOTE-045. The median follow-up was 62.9 months (range 58.6-70.9 months; data cut-off 1 October 2020). At 48 months, overall survival rates were 16.7% for pembrolizumab and 10.1% for chemotherapy; progression-free survival rates were 9.5% and 2.7%, respectively. The median duration of response (DOR) was 29.7 months (range 1.6+ to 60.5+ months) for pembrolizumab and 4.4 months (range 1.4+ to 63.1+ months) for chemotherapy; 36-month DOR rates were 44.4% and 28.3%, respectively. A total of 370 patients were enrolled in KEYNOTE-052. The median follow-up was 56.3 months (range 51.2-65.3 months; data cut-off 26 September 2020). The confirmed objective response rate was 28.9% (95% confidence interval 24.3-33.8), and the median DOR was 33.4 months (range 1.4+ to 60.7+ months); the 36-month DOR rate was 44.8%. Most treatment-related adverse events for pembrolizumab in either study were grade 1 or 2 and manageable, which is consistent with prior reports. CONCLUSION: With ∼5 years of follow-up, pembrolizumab monotherapy continued to demonstrate durable efficacy with no new safety signals in patients with platinum-resistant metastatic UC and as first-line therapy in cisplatin-ineligible patients. CLINICAL TRIAL REGISTRY AND ID: With ClinicalTrials.gov NCT02256436 (KEYNOTE-045); https://clinicaltrials.gov/ct2/show/NCT02256436 and NCT02335424 (KEYNOTE-052); https://clinicaltrials.gov/ct2/show/NCT02335424.	bladder
Use of an Application to Increase Self-Care Ability, Improve Quality of Life, and Decrease Stoma Complications in Patients With Ileocystoplasty or Ureterostomy Due to Bladder Cancer.	BACKGROUND: Quality of life for patients after ileocystoplasty or ureterostomy due to a urinary bladder neoplasm can be limited after discharge from the hospital. PURPOSE: To add the real-time communication ability of an application (app) to the daily care of this patient population to enhance communication between doctors and patients and provide improved nursing interventions, thus improving patients' self-care abilities and quality of life while decreasing stoma complications. METHODS: A total of 67 patients who underwent urinary tract diversion after total cystectomy were randomly divided into 2 groups. Patients in the control group (n = 32) received regular telephone follow-ups when they were discharged from the hospital, once a week for the first 2 months and then once a month for the next 22 months; patients in the intervention group (n = 35) used an app in addition to receiving regular telephone follow-ups. After 24 months of the intervention, multivariate analyses were conducted regarding self-care ability, complication rate, and quality of life. RESULTS: Self-care ability and quality of life scores in the intervention group were significantly improved during the 24-month period, and the complication rate was significantly reduced. CONCLUSION: Interaction via an app improved patients' self-care ability and quality of life. In addition, stoma complications were reduced. Future studies with larger sample sizes and patients of different ages are needed.	bladder
Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study.	OBJECTIVE: To develop the first Japanese real-world evidence of switch-maintenance avelumab in advanced, unresectable or metastatic urothelial carcinoma (aUC). METHODS: A multicenter-derived database registered 505 patients diagnosed with aUC between 2008 and 2021. Of these, 204 patients (40%) were selected and stratified according to the type of therapy used: maintenance avelumab group (27 [5.3%]), second-line (2 L) pembrolizumab group (103 [20%]) and 2 L cytotoxic chemotherapy group (74 [15%]). The progression-free survival and overall survival from the initiation of following therapy were compared. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors guideline v1.1 during the treatment period. A detailed analysis was performed in the maintenance avelumab group to investigate possible factors associated with response to avelumab therapy. RESULTS: The maintenance avelumab group had a longer overall survival, not progression-free survival, compared with the other two treatment groups. The median treatment-free interval between the last dose of first-line (1 L) chemotherapy and the initiation of avelumab therapy was 6 weeks (range, 3-22). Disease control rate of maintenance avelumab therapy in patients with a treatment-free interval of ≤6 weeks was higher than that in patients with a treatment-free interval of >6 weeks (77 vs 40%, P = 0.029). The patients showing objective response to 1 L chemotherapy were less likely to experience tumor relapse (4 of 19) after the initiation of avelumab therapy compared with those showing stable disease (7 of 8). CONCLUSIONS: Objective response to 1 L chemotherapy and early induction of maintenance avelumab therapy may be associated with increased benefit from maintenance avelumab therapy.	bladder
Sequential intravesical gemcitabine and docetaxel therapy in patients with nonmuscle invasive bladder cancer: a systematic review and meta-analysis.	PURPOSE OF REVIEW: Shortages in intravesical Bacillus Calmette-Guérin (BCG) immunotherapy represent a challenge in the management of high-risk nonmuscle invasive bladder cancer (HR-NMIBC). This study aimed to review the efficacy and safety of intravesical gemcitabine (GEM) and docetaxel (DOCE) for BCG-naive and unresponsive HR-NMIBC. RECENT FINDINGS: We identified six studies eligible for quantitative analysis through a systematic search according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. In the two studies in the BCG-naive setting, 1-year and 2-year pooled recurrence-free survival (RFS) were 86 and 84%, respectively. In the two studies in the BCG unresponsive setting, 6-month, 1-year and 2-year pooled high-grade recurrence-free survival (HG-RFS) were 80, 66 and 51%, respectively. Cumulative data from four studies revealed that 2.3% of patients could not complete induction therapy and 6.9% experienced treatment delay or dose reduction due to adverse events. SUMMARY: Despite the preliminary data and based on a small sample size, intravesical GEM/DOCE therapy is a highly promising combination yielding an effective and well tolerated alternative to BCG when indicated. Further large, well designed comparative studies with BCG are needed.	bladder
Prognostic nomogram based on the lymph node metastasis indicators for patients with bladder cancer: A SEER population-based study and external validation.	PURPOSE: This study aimed to compare the prognostic value of multiple lymph node metastasis (LNM) indicators and to develop optimal prognostic nomograms for bladder cancer (BC) patients. METHODS: BC patients were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015, and randomly partitioned into training and internal validation cohorts. Genomic and clinical data were collected from The Cancer Genome Atlas (TCGA) as external validation cohort. The predictive efficiency of LNM indicators was compared by constructing multivariate Cox regression models. We constructed nomograms on basis of the optimal models selected for overall survival (OS) and cause-specific survival (CSS). The performance of nomograms was evaluated with calibration plot, time-dependent area under the curve (AUC) and decision curve analysis (DCA) in three cohorts. We subsequently estimated the difference of biological function and tumor immunity between two risk groups stratified by nomograms in TCGA cohort. RESULTS: Totally, 10,093 and 107 BC patients were screened from the SEER and TCGA databases. N classification, positive lymph nodes (PLNs), lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) were all independent predictors for OS and CSS. The filtered models containing LODDS had minimal Akaike Information Criterion, maximal concordance indexes and AUCs. Age, LODDS, T and M classification were integrated into nomogram for OS, while nomogram for CSS included gender, tumor grade, LODDS, T and M classification. The nomograms were successfully validated in predictive accuracy and clinical utility in three cohorts. Additionally, the tumor microenvironment was different between two risk groups. CONCLUSIONS: LODDS demonstrated superior prognostic performance over N classification, PLN and LNR for OS and CSS of BC patients. The nomograms incorporating LODDS provided appropriate prediction of BC, which could contribute to the tumor assessment and clinical decision-making.	bladder
Diagnostic Accuracy of Clinical Lymph Node Staging for Upper Tract Urothelial Cancer Patients: A Multicenter, Retrospective, Observational Study.	PURPOSE: Treatment options for the management of upper tract urothelial cancer are based on accurate staging. However, the performance of conventional cross-sectional imaging for clinical lymph node staging (N-staging) remains poorly investigated. This study aims to evaluate the diagnostic accuracy of conventional cross-sectional imaging for upper tract urothelial cancer N-staging. MATERIALS AND METHODS: This study was a multicenter, retrospective, observational study. We included 865 nonmetastatic (M0) upper tract urothelial cancer patients treated with curative intended surgery and lymph node dissection who had been staged with conventional cross-sectional imaging before surgery. We compared clinical (c) and pathological (p) N-staging results to evaluate the concordance of node-positive (N+) and node-negative (N0) disease and calculate cN-staging's diagnostic accuracy. RESULTS: Conventional cross-sectional imaging categorized 750 patients cN0 and 115 cN+. Lymph node dissection categorized 641 patients pN0 and 224 pN+. The cN-stage was pathologically downstaged in 6.8% of patients, upstaged in 19%, and found concordant in 74%. The sensitivity and specificity of cN-staging were 25% (95% CI 20; 31) and 91% (95% CI 88; 93). Positive and negative likelihood ratios were 2.7 (95% CI 2.0; 3.8) and 0.83 (95% CI 0.76; 0.89). The area under the receiver operating characteristics curve (0.58, 95% CI 0.55; 0.61) revealed low diagnostic accuracy. CONCLUSIONS: Conventional cross-sectional imaging had low sensitivity in detecting upper tract urothelial cancer pN+ disease. However, cN+ increased the likelihood of pN+ by almost threefold. Thus, conventional cross-sectional imaging is a rule-in but not a rule-out test. Lymph node dissection should remain the standard during extirpative upper tract urothelial cancer surgery to obtain accurate N-staging. cN+ could be a strong argument for early systemic treatment.	bladder